A Systematic Review of Renal Pathology in Chronic Kidney Disease of Uncertain Etiology

Abstract

IntroductionDespite much research on chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka and the Mesoamerican nephropathy, the etiology and pathogenesis of this disease remains elusive. The pathology has broadly been described as chronic tubulointerstitial nephritis and no specific signature lesions have been identified.MethodsA scoping review was conducted through MEDLINE and Google Scholar databases for peer-reviewed publications on biopsy studies related to CKDu – Sri Lanka and Mesoamerican nephropathy to develop a comparative and critical analysis of the renal pathology found in these patients.ResultsThirteen studies met the selection criteria. Interstitial fibrosis was the predominant lesion in all the studies. Tubulointerstitial and glomerular abnormalities showed a more variable distribution. No characteristic histopathological feature was reported other than a proximal tubular lysosomal inclusion body which was claimed to indicate a toxic etiology. Three main pathogenetic mechanisms were postulated: repeated acute insults leading to scarring, low-grade chronic insults leading to non-inflammatory fibrosis, and tubulointerstitial damage in combination with glomerular injury. The main limitations in the interpretation and comparative analysis of these studies were the heterogeneity in case selection and biopsy reporting.ConclusionsAlthough no characteristic histopathological feature could be found in CKDu–Sri Lanka or Mesoamerican nephropathy, there are noticeable differences between these two groups in the frequency and severity of the glomerular and tubulointerstitial changes which warrant more explorative studies preferably on kidneys in early stages of the disease. Future strategies should ensure that more uniform selection criteria and reporting methods are used.